Stents having protruding drug-delivery features and associated systems and methods

ABSTRACT

Expandable elements having drug-delivery features and associated systems and methods are disclosed herein. In one embodiment, a drug-eluting stent includes a radially expandable cylindrical frame having a plurality of struts. The frame is transformable between a low-profile delivery state and an expanded deployed state. A plurality of drug-delivery features are carried by one of the struts and configured to deliver a drug to a treatment site within the patient or piercing through the tissue wall to break the constricting of the vessel wall inwardly. When the frame is in the expanded state within a body lumen of the patient, the drug-delivery features extend radially outwardly away from the strut and are configured to engage and, in some arrangements, pass through a wall of the body lumen.

CROSS-REFERENCE TO RELATED APPLICATION

This application claims the benefit of U.S. Provisional Application No.62/240,320 filed on Oct. 12, 2015, entitled DRUG-ELUTING STENTS HAVINGPROTRUDING DRUG-DELIVERY FEATURES AND ASSOCIATED SYSTEMS AND METHODS,which is herein incorporated by reference in its entirety.

TECHNICAL FIELD

The present technology relates generally to expandable elements, such asstents or scaffolds having spikes, flails, or other protruding featuresfor delivering drugs and/or penetrating target tissue within a humanpatient.

BACKGROUND

A variety of devices can be used to deliver drugs at desired treatmentlocations within a patient. For example, a drug-eluting stent (DES) canbe positioned at the location of a stenosis (arterial narrowing) causedby arteriosclerosis. DESs generally include a drug containing polymercoated over a metal stent or scaffold, or a bioresorbable stent orscaffold composed of a drug-containing polymer. After a DES is deliveredto a treatment location within a body lumen, it is expanded against avessel wall and the drug is released via direct contact with the wall.Direct delivery of the drug to the vessel wall enables significantlylower doses than those required via other delivery means (e.g., pills orinjections). However, depending on the design of the underlying stent orscaffold, 85% or more of the stented vessel wall area may not be incontact with the stent struts. Accordingly, significant diseasedportions of the vessel wall may not receive a desired dose or deliveryof the drug will not be uniform throughout the treatment site.Additionally, portions of the DES may be in contact with blood, arterialplaque and/or with other fluid or materials within the vessel lumen thatare not intended delivery sites for the drug. These issues can result indrug tissue concentrations that are lower than desired or less uniformthan desired.

Drug-eluting balloons (DEBs), and non drug-eluting balloons, provide analternative to DESs, and can address some of the limitations discussedabove. For example, DEBs can also be delivered to a desired treatmentlocation and expanded against a vessel wall to release a drug. DEBs,however, can include a coating of the drug over an entire surface areaof the balloon that expands to be in uniform contact with the vesselwall. Accordingly, DEBs can provide a more uniform dose to the adjacentvessel tissue. Additionally, when used in conjunction with angioplasty,the drug can be delivered at the location and time of any vessel damagethat occurs during the procedure. Even so, DEBs also have severallimitations. For example, during the delivery of the drug (i.e., whenthe balloon is inflated), blood flow in the associated vessel is stoppedor severely obstructed, and no other treatment devices can be passedthrough the vessel. Additionally, both DEBs and existing DESs fail toprovide drug-delivery at all locations along an adjacent vessel wall.Specifically, uneven vessel walls, obstructions, contours, or otherfeatures can prevent the balloon surface or stent struts from reachingportions of the vessel wall. Moreover, existing DESs and DEBs do notprovide for drug-delivery into the vessel wall (i.e., penetration of thevessel wall for drug-delivery within the tissue itself).

BRIEF DESCRIPTION OF THE DRAWINGS

Many aspects of the present technology can be better understood withreference to the following drawings. The components in the drawings arenot necessarily to scale. Instead, emphasis is placed on illustratingclearly the principles of the present technology. For ease of reference,throughout this disclosure identical reference numbers may be used toidentify identical or at least generally similar or analogous componentsor features.

FIG. 1 is a partially schematic side view of a portion of a drugdelivery system in a delivery state (e.g., low-profile or collapsedconfiguration) within a body lumen and configured in accordance with anembodiment of the present technology.

FIG. 2A is a side view of the portion of the drug delivery system ofFIG. 1 in a partially deployed state (e.g., expanded configuration)within the body lumen and configured in accordance with an embodiment ofthe present technology.

FIG. 2B is a cross-sectional view of a portion of the drug deliverysystem of FIG. 2A taken along line 2B-2B.

FIGS. 3A-3D are isometric views of portions of drug-eluting expandablestructures having drug-delivery features configured in accordance withembodiments of the present technology.

FIG. 4 is a cross-sectional view of a portion of a drug-eluting stentillustrating a drug-delivery feature configured in accordance with yetanother embodiment of the present technology.

FIGS. 5A-5C are cross-sectional images of a portion of a blood vesselhaving a drug-eluting stent configured in accordance with an embodimentof the present technology expanded therein.

FIGS. 6A-6O are cross-sectional images of a portion of a blood vesselhaving a drug-eluting stent with square struts configured in accordancewith another embodiment of the present technology expanded therein.

FIGS. 7A-7C are cross-sectional images of a portion of a blood vesselhaving a drug-eluting stent with round struts configured in accordancewith yet another embodiment of the present technology expanded therein.

FIGS. 8A-8H are cross-sectional images of a portion of a blood vesselhaving a drug-eluting stent with pointed struts configured in accordancewith still another embodiment of the present technology expandedtherein.

FIGS. 9A-9K are cross-sectional images of a portion of a blood vesselhaving a drug-eluting stent with square struts configured in accordancewith an embodiment of the present technology expanded near anatherosclerotic lesion therein.

DETAILED DESCRIPTION

The following disclosure describes various embodiments of expandablestructures, such as stents or scaffolds, having spikes, flails, or otherprotruding features for delivering drugs and/or penetrating targettissue within a human patient, and associated systems and methods. Thedrug-delivery features can be integrally formed with expandable element,or may include separate features protruding from a strut or other memberof the expandable element positioned to engage and/or penetrate a vesselwall. For example, several embodiments configured in accordance with thepresent technology include expandable structure with drug-deliveryfeatures for delivering drugs to deep intimal layers and/or mediallayers of vessels. In some embodiments, the drug-delivery features caninclude spikes protruding from one or more struts or portions of theexpandable structure. The spikes can be configured to penetrate thevessel wall. In additional embodiments, the drug-delivery features caninclude angular protrusion(s) extending from one or more struts. Suchangular protrusions are expected to provide better contact with thevessel wall, moving past obstructions or other interfering material tomore effectively deliver drugs to target tissue. Additionally, theangular protrusions can increase the surface area of the drug-deliveryfeatures in contact with the vessel wall, thereby providing for a moreuniform delivery of the drug. Still other embodiments may eliminateparticular components and/or procedures.

Certain details are set forth in the following description and FIGS.1-9K to provide a thorough understanding of various embodiments of thedisclosure. To avoid unnecessarily obscuring the description of thevarious embodiments of the disclosure, other details describingwell-known structures and systems often associated with expandablestructures, drug-delivery features, and the components or devicesassociated with the manufacture of such structures are not set forthbelow. Moreover, many of the details and features shown in the Figuresare merely illustrative of particular embodiments of the disclosure.Accordingly, other embodiments can have other details and featureswithout departing from the spirit and scope of the present disclosure. Aperson of ordinary skill in the relevant art will therefore understandthat the present technology, which includes associated devices, systems,and procedures, may include other embodiments with additional elementsor steps, and/or may include other embodiments without several of thefeatures or steps shown and described below with reference to FIGS.1-9K. Furthermore, various embodiments of the disclosure can includestructures other than those illustrated in the Figures and are expresslynot limited to the structures shown in the Figures.

I. DRUG-ELUTING STENTS AND OTHER STRUCTURES AND ASSOCIATED SYSTEMS ANDMETHODS

FIG. 1 is a partially schematic side view of a portion of a drugdelivery system 100 (“the system 100”) configured in accordance with anembodiment of the present technology. In the arrangement shown in FIG.1, the system 100 is in a delivery state (e.g., low-profile or collapsedconfiguration) within a body lumen 102 (e.g., blood vessel) of a humanpatient. The system 100 includes, for example, a catheter 104 and adrug-eluting stent 106 carried in a delivery/collapsed state within adistal portion of the catheter 104. Although a stent is illustrated, itwill be appreciated that embodiments of the present technology can alsoinclude cages, meshes, balloons, membranes, tubular structures,circumferential bodies, expandable elements, expandable membranes,expandable structures, expandable tubular structures, andcircumferentially expandable catheter tips with and without guidewirelumens.

The catheter 104 is configured for intravascular delivery through thebody lumen 102 to position the drug-eluting stent 106 at a desiredtreatment location. Additionally, several embodiments can provide fordetachment of a stent or other structure including the drug-deliveryfeatures. For example, in several embodiments, a wire or attachmentmember can release the stent 106 via mechanical, thermal, electrical orother means. In some embodiments, the drug-eluting stent 106 can beoperatively coupled to a circular or non-circular longitudinal memberconfigured to release and/or recapture the drug-eluting stent 106 in thesystem 100. The member can be coupled, either directly or indirectly, toa frame (111 of FIG. 2A) of the drug-eluting stent. In some of theseembodiments, the stent 106 or other structure can be designed forpermanent placement within a patient.

FIG. 2A is a partially schematic side view of the system 100 of FIG. 1in a partially deployed state (e.g., expanded configuration) within thebody lumen 102. In the illustrated embodiment of FIG. 2A, thedrug-eluting stent 106 has been advanced from a distal end of thecatheter 104 and positioned adjacent a desired treatment site. The stent106 includes a plurality of struts 204 forming a radially expandablecylindrical frame 111 and members engaging with and extending betweentwo or more rows of struts. As illustrated, the struts 204 of theexpanded drug-eluting stent 106 are in apposition with the walls of thebody lumen 102. Referring to the blown-up portions of FIG. 2A, thedrug-eluting stent 106 further includes a plurality of drug-deliveryfeatures 206 carried by the struts 2204. Several embodiments can bedesigned for application of a drug onto the stent or the drug-deliveryfeatures that are configured to receive a drug and release the drug oncethe stent is expanded at the desired treatment site. FIG. 2B is across-sectional view of a portion of the drug delivery system of FIG. 2Ataken along line 2B-2B. As illustrated in FIG. 2B, the drug-elutingstent 106 includes a plurality of struts 204 having plurality ofdrug-delivery features 206 carried by the struts 204. The drug-deliveryfeatures 206 are integrally formed portions of the struts 204, disposedacross at least a portion of an outer dimension of the stent 106, andextending radially outward away from the stent 106 toward the targetportion of the body lumen.

The drug-eluting stent 106 can be a self-expanding structure. In otherembodiments, the drug-eluting stent 106 can be coupled to a balloon orother suitable techniques and/or structures known to those of skill inthe art may be used to transform the drug-eluting stent 106 from thelow-profile delivery state to the deployed/expanded state shown in FIG.2A. In addition, the drug-eluting stent 106 can be operatively coupledto an actuation mechanism, such as a mechanical actuation mechanism,configured to position, expand, retract, re-position, and/or remove thedrug-eluting stent 106.

The frame 111, struts 204, and/or drug-delivery features 112 can becomposed of or formed from a variety materials including, e.g., nitinol,cobalt chromium, stainless steel, any of a variety of other metals ormetal alloys, or a combination thereof. The frame 111, struts 204,and/or drug-delivery features 112 may also be composed of or formed frombioresorbable biodegradable, nanoporous or non-bioresorbable,non-biodegradable, non-nanopourous materials including, e.g., one ormore polymers, plastic materials, etc., or a combination thereof. Insome embodiments, the frame 111 and the struts 204 can be formed from abioresorbable material and the drug-delivery features 112 can be formedfrom a non-bioresorbable material, such as nitinol. In theseembodiments, the drug-delivery features 112 can remain engaged with orpenetrating a portion of the body lumen after the expanded frame 111 andstruts 204 bio-resorb. After the expanded frame 111 and struts 204bio-resorb, the body lumen where the drug-eluting stent 106 had beenexpanded is no longer partially occluded by the frame 111 and the struts204 allowing for larger volumes of fluids, such as aqueouspharmaceutical compositions, to pass through the body lumen and contactthe luminal wall. The drug-delivery features 112 may also be formed of abio-resorbable material and, once the drug-eluting stent 106 hasbio-resorbed, the spaces in the body lumen wall vacated by thedrug-delivery features 112 can be contacted by the fluids passingthrough the lumen. In this way, the drug-eluting stent 106 can increasea surface area of the lumen wall contacted by the fluid.

The material(s) for forming the frame 111, struts 204, and/ordrug-delivery features 112 can be selected based on mechanical and/orthermal properties, such as strength, ductility, hardness, elasticity,flexibility, flexural modulus, flexural strength, plasticity, stiffness,emissivity, thermal conductivity, specific heat, thermal diffusivity,thermal expansion, any of a variety of other properties, or acombination thereof. If formed from a material having thermalproperties, the material can be activated to deliver thermal treatmentto the desired treatment site.

Regardless of the material, the frame 111, struts 204, and/ordrug-delivery features 112 can be formed from a tube or a wire, such asa solid wire, by laser cutting or other suitable techniques. When formedfrom the wire, a portion of the wire can be removed by chemical etchingor another suitable method to create an inner dimension of thedrug-eluting stent 106.

In accordance with the present technology, drug-eluting stents 106(e.g., the frame 111 and the struts 204) can be sized and shaped forplacement within various body lumens, including blood vessels, while notrupturing the vessel. For example, several stents and other structuresconfigured in accordance with the present technology can have radialstrength that allows for features of the body lumen (e.g., vessel wall)to receive drugs without dissection or damage thereto. Vessels in whichthe drug-eluting stents 106 may be sized and shaped for placementinclude arteries, such as coronary arteries, peripheral arteries,carotid arteries, circle of willis, anterior cerebral artery, middlecerebral artery, posterior cerebral artery, any of the lenticulostriatearteries, renal arteries, femoral arteries, veins, such as cerebralveins, saphenous veins, arteriovenous fistulas, or any other vessel thatmay contain a treatment site. Drug-eluting stents 106 can have a varietyof shapes, including a cube, a rectangular prism, a cylinder, a cone, apyramid, or variations thereof.

The stent 106 and other structures having drug-delivery featuresconfigured in accordance with the present technology can include avariety of dimensions (in both the low-profile delivery state andexpanded deployed state). These embodiments can provide for expansionthat enables usage in a variety of situations covering a wide range ofdimensions. Regardless of the shape, drug-eluting stents 106 can have alength of about 0.25 mm, about 0.5 mm, about 1 mm, about 2 mm, about 3mm, about 4 mm, about 5 mm, about 6 mm, about 7 mm, about 8 mm, about 9mm, about 10 mm, about 12 mm, about 14 mm, about 16 mm, about 18 mm,about 20 mm, about 30 mm, about 40 mm, about 50 mm, about 60 mm, about70 mm, about 80 mm, about 90 mm, or about 100 mm. In addition, adrug-eluting stent 106 shaped into a cube, a rectangular prism, or apyramid can have a width of about 0.25 mm, about 0.5 mm, about 1 mm,about 2 mm, about 3 mm, about 4 mm, about 5 mm, about 6 mm, about 7 mm,about 8 mm, about 9 mm, about 10 mm, about 12 mm, about 14 mm, about 16mm, about 18 mm, about 20 mm, about 25 mm, or about 30 mm. Moreover, adrug-eluting stent 106 shaped into a cylinder or a cone can have adiameter of about 0.25 mm, about 0.5 mm, about 1 mm, about 2 mm, about 3mm, about 4 mm, about 5 mm, about 6 mm, about 7 mm, about 8 mm, about 9mm, about 10 mm, about 12 mm, about 14 mm, about 16 mm, about 18 mm,about 20 mm, about 25 mm, about 30 mm, about 35 mm, about 40 mm, orabout 50 mm. The width or the diameter of the drug-eluting stent 106 candecrementally decrease along a length of the stent. In addition, thedrug-eluting stent 106 can be sized and shaped to prepare the body lumenfor certain procedures, such as a drug-eluting stent placementprocedure.

Profiles of the drug-eluting stents or other structures can be sizedsuch that the drug-eluting stents or other structures are compatiblewith a wide range of catheter sizes. Embodiments in accordance with thepresent technology can include drug-eluting stents or other structuresdesigned to receive a guidewire, such as guidewires having a diameter of0.010, 0.014, 0.018, 0.035, or 0.038 inch. In several embodiments, thestent or scaffold structure can be sized and designed for delivery via amicro-catheter that it is pushed through. In some embodiments, stents orstructures configured in accordance with the present technology can beincorporated into a delivery system, including modular or single unitdelivery systems.

The drug-eluting stent 106 can include a marking for visualization ofthe stent 106 within the body lumen, such as one or more radiopaquemarkers. The radiopaque markers can be formed from Clearfil Photo CorePLT®, tantalum, titanium, tungsten, barium sulfate, and zirconium oxide,or another suitable radiopaque marking. The markings can be formed on aproximal portion of the drug-eluting stent 106, a distal portion, anintermediate portion, or a combination thereof. The markings can be aband, a coil, a clip, filled into one or more portions of a tube in thestent, plated onto one or more portions of the stent, or a combinationthereof. Regardless of the type of marking, the marking can be coined,swaged, wrapped, or encased along, or onto any portion of the stent.

Stents and other structures configured in accordance with the presenttechnology can be flexible enough to track through various anatomicalfeatures, including those having a curvature. The flexible properties ofthe stent and other structures can be provided by the material from theyare formed. In addition, flexible properties can also be provided byfracturing one or more of the members engaging with and extendingbetween two or more rows of struts. Additionally, the drug-eluting stentor other structure can be readily deployed and expanded, and retractedand contracted. The drug-eluting stent or other structure can also bereadily repositioned within a vessel or other lumen.

II. DRUG-DELIVERY FEATURES OF DRUG-ELUTING STENTS AND OTHER STRUCTURESAND ASSOCIATED SYSTEMS AND METHODS

In the embodiment shown in FIG. 2, the drug-eluting stent 106 includesdrug-delivery features 206 carried by the strut 204. The drug-deliveryfeatures 206 may also be carried by more than one strut 204, the frame111, or a combination thereof. The drug-delivery features 206 may beintegrally formed with the struts 204, for example by bending ortwisting a portion of one or more struts and/or the frame 111 away froma longitudinal axis of the stent 106 or, alternatively, thedrug-delivery features 206 may be separate, discrete components that areattached to desired locations along the struts 204 and/or the frame 111.As illustrated, the drug-delivery features 206 are integrally formedwith the struts 204. However, as described below with reference to FIGS.3A-3D, the drug-delivery features 206 may have a variety of differentshapes, sizes, and configurations. The drug-delivery features disclosedherein enhances engagement with and/or penetration of the lumen wall,provides enhanced drug-delivery, and allows for better treatment at thedesired location. In other embodiments, such as non drug-deliverystents, the drug-delivery features 206 can be protruding members.

In several embodiments, a drug-eluting compound is coated onto at leasta portion of the drug-delivery features. The drug-eluting compound canbe a synthetic or biological polymer coated into a variety of differentpatterns and thicknesses suitable for delivering the drug containedtherein. In other embodiments, the drug-delivery features themselves maybe composed of drug-eluting materials. The drug carried by thedrug-eluting compound and/or the drug-delivery features in accordancewith the present technology can be any drug suitable for treating thetreatment site in which the drug-eluting stent will be placed and may ormay not include an excipient. For example, the drug can be ananti-proliferative, an anti-neoplastic, a migration inhibitor, anenhanced healing factor, an immunosuppressive, an anti-thrombotic, ablood thinner, or a radioactive compound. Examples of anti-neoplasticsinclude, but are not limited to, siroliums, tacrolimus, everolimus,leflunomide, M-prednisolone, dexamethasone, cyclosporine, mycophenolicacid, mizoribine, interferon, and tranilast. Examples ofanti-proliferatives include, but are not limited to, taxol/paclitaxel,actinomycin, methotrexate, angiopeptin, vincristine, mitmycine, statins,c-myc antisense, Abbot ABT-578, RestinASE, 2-chloro-deoxyadenosine, andPCNA ribozyme. Examples of migration inhibitors, but are not limited to,include batimistat, prolyl hydrosylase, halofunginone, c-preteinaseinhibitors, and probucol. Examples of enhanced healing factors include,but are not limited to, BCP 671, VEGF, estradiols, NO donor comounds,and EPC antibodies. Examples, of radioactive compounds include, but arenot limited to, strontium-89 chloride (Metastron®), samarium-153(Quadramet®), radium-223 dichloride (Xofigo®), yttrium-90, andiodine-131. In some embodiments, the drug-eluting compound and/or thedrug-delivery features can carry more than one drug.

FIGS. 3A-3D are isometric views of portions of protruding members, suchas drug-delivery features, carried by drug-eluting stents configured inaccordance with additional embodiments of the present technology. Theseprotruding members may be used with the drug-eluting stent 106 describedabove with reference to FIGS. 1 and 2, or other suitable drug-elutingand non drug-eluting stents configured in accordance with the presenttechnology. FIG. 3A, for example, illustrates a portion of a stent 300including a frame 302 and a plurality of struts 304 having protrudingmembers 306 (e.g., spikes, sharpened/tapered members, barbs, needles)configured to engage with and/or penetrate a portion of the body lumen,such as a vessel (not shown). The protruding members 306 are integrallyformed portions of the struts 304 and extend radially outward away fromthe stent 300 toward the target portion of the body lumen. In theembodiment illustrated in FIG. 3B, for example, a drug-eluting stent 310includes a strut 312 having drug-delivery features 314 carried thereon.In this embodiment, the drug-delivery features 314 are pointed conicalprotrusions. In some embodiments, the pointed conical protrusions canprovide for penetration through a body lumen wall (e.g., a vessel wall)to deliver drugs directly into target tissue beyond the vessel wall.Vessels and target tissues are described above with reference to FIGS.2A and 2B. FIG. 3C illustrates a portion of a drug-eluting stent 320with a strut 322 carrying drug-delivery features 324. In thisembodiment, the drug-delivery features 324 are pointed conicalprotrusions having ribbed surfaces and flattened tops. In someembodiments, the textured (e.g., ribbed) surfaces of the protruding andconical drug-delivery features 324 are expected to provide greatersurface area for drug-delivery. While only illustrated on conicaldrug-delivery features 324, any drug-delivery features can include atextured surface such as a ribbed surface (vertical, horizontal, radial,or circular relative to a longitudinal plane of the drug-deliveryfeature), a cross-hatched surface, an isotropic surface, or othersurface types suitable for providing greater surface area fordrug-delivery. FIG. 3D illustrates a portion of a drug-eluting stent 330including a strut 332 carrying drug-delivery features 334. In theillustrated embodiment, drug-delivery features 334 are wedge shapedprotrusions configured to engage/penetrate through a vessel wall fordrug-delivery.

Although the illustrated embodiments of FIGS. 2 and 3A-3D includeprotruding members, such as, drug-delivery features having a variety ofshapes, it is to be understood that other embodiments can includedrug-delivery features having alternative shapes to those shown in theseFigures. For example, the drug-delivery features can be sized and shapedfor placement within various body lumens, including vessels as describedherein. The sizes and shapes can be selected to achieve a desiredengagement with or penetration of certain features (e.g., targettissues) of the body lumen in which the drug-eluting stent 106 will beplaced. The drug-delivery features can have a number of shapes,including but not limited to, a cube, a square, a rectangular prism, acylinder, a circle, a cone, a pyramid, curved-spikes, or other pointedshape. Any of these shapes can have flat, dull, pointed, and/or sharpdistal portions.

The drug-delivery features can be sized and shaped to engage with and/orpenetrate an occlusion, a neointima, an intima, an internal elasticlamina (IEL) a media, an external elastic lamina (EEL), an adventitia,or a combination thereof. The drug-delivery features can also be sizedand shaped to engage with and/or penetrate a tissue and/or structureadjacent to the body lumen in which the drug-eluting stent 106 is to beplaced while not rupturing the body lumen. For example, the drug-elutingstent 106 can include square drug-delivery features sized and configuredto penetrate into the intima and/or the media of a body lumen, pointeddrug-delivery features sized and configured to penetrate and extend intothe media, and/or the IEL In addition, drug-delivery features can beconfigured to bend in one or more directions relative to a longitudinalaxis of the drug-eluting stent to engage with and/or penetrate a portionof the body lumen described herein. In several embodiments, thedrug-delivery features can penetrate deeper into the wall of a diseasedbody lumen, such as a vessel, compared to a stent lacking drug-deliveryfeatures. In addition, the drug-eluting stent can allow for blood toflow even while in the expanded position and with drug-eluting on-going.

Various drug-delivery features described herein can deliver drugs deeperinto a vessel wall than possible via angioplasty balloons or otherexisting devices. In addition to carrying one or more drugs fortreatment of the site, the drug-delivery features can also carry amolecule suitable for degrading a portion of the occlusion, neointima,and/or intima to allow the drug-delivery features to penetrate deeper into the vessel wall than without the molecule. For example, the moleculesuitable for degradation can be an enzyme, such as elastase,collagenase, or a proteinase, such as, metalloproteinases, serineproteinases, cysteine proteinases, extracellular sulfatases,hyaluronidases, lysyloxidases, lysyl hydroxylases, or a combinationthereof.

Further, it will also be appreciated that drug-eluting stents configuredin accordance with the present technology can carry one or moredrug-delivery features on one or more portions of the stent. Forexample, the drug-eluting stents can carry about 5 drug-deliveryfeatures, about 10 drug-delivery features, about 15 drug-deliveryfeatures, about 20 drug-delivery features, about 30 drug-deliveryfeatures, about 40 drug-delivery features, about 50 drug-deliveryfeatures, about 60 drug-delivery features, about 70 drug-deliveryfeatures, about 80 drug-delivery features, about 90 drug-deliveryfeatures, or about 100 drug-delivery features. The drug-deliveryfeatures can be carried by the frame 111, the struts 204, or acombination thereof. The number of drug-delivery features can varydepending upon, for example, the target treatment site, the type of drugbeing delivered, and size of the stent, etc. In addition, thedrug-delivery features carried by the stent can be different types ofthe drug-delivery features disclosed herein.

FIG. 4 is a cross-sectional view of a portion of a drug-eluting stent400 including a strut 402 carrying drug-delivery feature 404 configuredin accordance with yet another embodiment of the present technology. Inthe illustrated embodiment, the drug-delivery feature 404 includes areservoir 406, and a drug 408 carried by the reservoir 406. Thereservoir 406 can at least partially contain the drug 408 and protect itfrom being prematurely released (e.g., via scraping during delivery ofthe associated stent through a catheter). Once positioned against a bodylumen wall (e.g., a vessel wall), tissue and/or fluid can interact withthe drug-delivery feature 404 to dissolve the drug 408 and selectivelyrelease it from the reservoir 406. In other embodiments, thedrug-delivery feature can be configured to deliver the drug via avariety of means once the drug-eluting stent is expanded. Drug-deliveryfeature 404 is accordingly expected to provide an effective means forselectively delivering a drug to a desired location, while reducinginadvertent loss or release of drugs. In other embodiments, thedrug-eluting stent can include more than one drug-delivery feature, or adrug-delivery feature having more than one reservoir. In severalembodiments, the stent including drug-delivery features configured inaccordance with the present technology can have the drug-deliveryfeature, such as the coating or the reservoir, concealed (e.g.,recessed) until the stent is positioned at the treatment site. Oncepositioned at the target site, the drug-delivery feature can be revealed(e.g., expanded/projected, etc.) during and/or after expansion of thestent. This is expected to reduce any loss of the drug carried by thedrug-delivery feature during delivery to the treatment site.

In some embodiments, the drug-eluting stents can further include amaterial (e.g., PTFE, Dacron, polyamides, such as nylon and/orpolyurethane based materials, silicone, etc.) positioned over a stent,scaffold or other structure having drug-delivery features covering atleast a portion of the outer surface area. In some embodiments, thematerial covers the entire outer surface area. The material can be amesh or a braid. In some embodiments, the material can be configured toincrease a surface area of the stent useful for providing additionalsurface area of the stent for coating with a drug. In other embodiments,the material can further be configured to allow blood flow through theinner diameter of the stent and/or limit blood flow to an outerdimension of the stent. In additional embodiments, the material cancreate a barrier between fluid flow (e.g., blood flow) and thedrug-delivery locations. In addition, the material can be configured toprevent debris from the wall of the body lumen from entering thebloodstream. In such embodiments, the associated systems and devices canbe used for temporary dissection tacking or coverage of a region thatmay have been perforated during a procedure.

III. ADDITIONAL EMBODIMENTS OF STENTS AND OTHER STRUCTURES ANDASSOCIATED SYSTEMS AND METHODS

The embodiments described herein provide a structure with a means fordelivering drugs to a specific region within a body lumen, such as thevasculature, while still allowing fluid (e.g., blood) to flow throughthe treatment area where the structure has been placed and/or otherdevices or treatment means within the adjacent body lumen. In someembodiments, the drug-eluting stents are configured not to limit fluidflow (e.g., blood flow) through the body lumen (e.g., vessel). Inaddition, the stent can be configured to prepare the body lumen fortreatment, by raking the stent, pulling the stent, turning the stent, ora combination thereof, proximal or distal to the treatment site. Inother embodiments, the drug-eluting stent can be configured to rotatewhen mechanical force is applied.

The systems disclosed herein can provide for adjustment, recapture, andredeployment of the associated stents or other structures, allowing apractitioner to more effectively to treat a desired region moreaccurately and deliberately. In several embodiments, the stent or otherdelivery structure can be deployed for a temporary period (e.g., forless than 24 hours), and then retracted and removed. The drug-elutingstent can also be configured to post-dilate when removed from the bodylumen. In other embodiments, the stent or other delivery structure canbe deployed for a long-term temporary period (e.g., for less than 2weeks, less than one month, less than 6 months, less than one year), andthen retracted and removed. In some embodiments, a different stent ordelivery structure can be deployed after a first stent or deliverystructure has been retraced and removed. The duration of deployment andduration after removal before deployment of the different stent ordelivery structure can vary from minutes, to hours, to days, to weeks,to months, or to years. In these embodiments, removal of the first stentor delivery structure and deployment of a different stent or deliverystructure can occur once, twice, three times, four times, five times,six times, seven times, eight times, nine times, or ten times. Moreover,the embodiments described herein can allow for a lower profile systemthan currently available balloons.

While many embodiments of the stents and/or structures described hereininclude drug-eluting stents, additional embodiments of the expandableelements, such as stents and/or structures, can include non drug-elutingstents and/or non drug-eluting structures. In these embodiments, the nondrug-eluting stents may include one or more protruding members, such asspikes. The spikes can be configured to engage with and/or penetrate aportion of the body lumen or vessel. For example, the spikes canpenetrate the vessel wall, thereby reducing and/or eliminating anelasticity of the vessel wall. In these embodiments, the protrudingmembers can be configured to prevent the vessel wall from progressinginward toward the lumen and restricting and/or constricting flowtherein. The protruding members can be integrally formed with thestruts, or disposed on the surface of the struts, extending radiallyoutward from the struts toward the target tissue.

IV. ADDITIONAL EXAMPLES

The following examples are illustrative of several embodiments of thepresent technology. In these examples, a drug-eluting stent was placedwithin a vessel of a human patient post mortem. Three different types ofstents were used: (a) a metal stent having square drug-deliveryfeatures, (b) a metal stent having round drug-delivery features, and (c)a metal stent having sharpened/tapered drug-delivery features. Stentshaving square or rectilinear drug-delivery features measured about 115μm by 100 μm, stents having round or rounded drug-delivery featuresmeasured about 650 μm in diameter, and stents having sharpened/tapereddrug-delivery features measured about 870 μm long and about 193 μm wideat the widest portion.

A. Example 1—Stents Having Sharpened/Tapered Drug-Delivery FeaturesEngage with the External Elastic Lamina

In this example, a stent having sharpened/tapered drug-delivery featureswas placed within a blood vessel of a human cadaver. Following placementof the sharpened/tapered drug-delivery feature stent, the vessel wasremoved from the cadaver, embedded in plastic, and sliced intocross-sections of a thickness suitable for histology. The cross-sectionswere stained using an Elastic Masson Trichrome stain, imaged, andevaluated for the positioning of the pointed drug-delivery feature stentin the vessel.

FIGS. 5A-5C include histology images taken after placement of the stenthaving the sharpened/tapered drug-delivery features within the vessel ofthe cadaver. FIG. 5A, for example, depicts a sharpened/tapereddrug-delivery feature penetrated through the neointima, IEL, media, andengaging with the EEL. FIG. 5B depicts a sharpened/tapered drug-deliveryfeature penetrated through the neointima, IEL, and into the media. FIG.5C depicts a sharpened/tapered drug-delivery feature penetrated throughthe neointima, IEL, media, and engaging with the EEL. None of thedrug-delivery features described above in Example 1 perforated thevessel.

B. Example 2—Stents Having Square Drug-Delivery Features

In this example, a stent having square or rectilinear drug-deliveryfeatures was placed within a blood vessel of a human cadaver. Followingplacement of the square drug-delivery feature stent, the vessel wasremoved from the cadaver, embedded in plastic, and sliced intocross-sections of a thickness suitable for histology. The cross-sectionswere stained using an Elastic Masson Trichrome stain, imaged, andevaluated for the positioning of the square drug-delivery feature stentin the vessel.

FIGS. 6A-6O include histology images taken after placement of the stenthaving the square drug-delivery features in a vessel of the cadaver. Forexample, FIG. 6A depicts a square drug-delivery feature having a widthof 96.79 μm and a depth of 115.62 μm. FIGS. 6B and 6C depict two squaredrug-delivery features with one engaging with the neointima and onepushing the neointima into the IEL FIG. 6D depicts one squaredrug-delivery feature with one engaging with the neointima and oneengaging with the media. FIG. 6E depicts one square drug-deliveryfeature with one engaging with the neointima. FIG. 6F depicts threesquare drug-delivery features with one engaging with the neointima.FIGS. 6G and 6H depict square drug-delivery features pushing theneointima into the IEL. FIG. 6I depicts one square drug-delivery featureengaging with the IEL. FIG. 6J depicts square drug-delivery featurespenetrating the neointima and others pushing the neointima into the IELFIG. 6K depicts a square drug-delivery feature engaging with theneointima. FIG. 6L depicts square drug-delivery features penetrating theneointima. FIG. 6M depicts square drug-delivery features engaging theneointima and others penetrating into the intima engaging with the IEL.FIG. 6N depicts square drug-delivery features engaging the neointima.FIG. 6O depicts square drug-delivery features engaging the neointima andothers penetrating into the media. None of the drug-delivery featuresassociated with Example 2 perforated the vessel.

C. Example 3—Stents Having Round Drug-Delivery Features

In this example, a stent having round or rounded drug-delivery featureswas placed within a blood vessel of a human cadaver. Following placementof the round drug-delivery feature stent, the vessel was removed fromthe cadaver, embedded in plastic, and sliced into cross-sections of athickness suitable for histology. The cross-sections were stained usingan Elastic Masson Trichrome stain, imaged, and evaluated for thepositioning of the round drug-delivery feature stent in the vessel.

FIGS. 7A-7C include histology images taken after placement of the stenthaving round drug-delivery features in a vessel of the human patient.FIG. 7A depicts a round drug-delivery feature having a diameter of651.41 μm. FIG. 7B depicts a round drug-delivery feature engaging withthe neointima and pushing the neointima into the IEL. FIG. 7C depicts around drug-delivery feature engaging with the neointima and otherspenetrating into the media. None of the drug-delivery featuresassociated with Example 3 perforated the vessel.

D. Example 4—Stents Having Sharpened/Tapered Drug-Delivery Features

In this example, a stent having sharpened/tapered drug-delivery featureswas placed within a blood vessel of a human cadaver. Following placementof the sharpened/tapered drug-delivery feature stent, the vessel wasremoved from the patient, embedded in plastic, and sliced intocross-sections of a thickness suitable for histology. The cross-sectionswere stained using an Elastic Masson Trichrome stain, imaged, andevaluated for the positioning of the sharpened/tapered drug-deliveryfeature stent in the vessel.

FIGS. 8A-8H include histology images taken after placement of the stenthaving the sharpened/tapered drug-delivery features in a vessel of thecadaver. FIG. 8A, for example, depicts a sharpened/tapered drug-deliveryfeature having a maximum width of 193.32 μm and a length of 868.88 μm.FIG. 8B depicts a sharpened/tapered drug-delivery feature penetratingthrough the neointima, through the IEL, and engaging with the media.FIGS. 8C and 8D depict a sharpened/tapered drug-delivery featurepenetrating through the neointima, through the IEL, through the media,and engaging the EEL. FIG. 8E depicts a sharpened/tapered drug-deliveryfeature penetrating through the neointima, through the IEL, and engagingthe media. FIG. 8F depicts a sharpened/tapered drug-delivery featureengaging the neointima. FIG. 8G depicts a sharpened/tapereddrug-delivery feature penetrating through the neointima, through theIEL, through the media, and engaging the EEL. FIG. 8H depicts asharpened/tapered drug-delivery feature penetrating through theneointima, through the IEL, and penetrating the media. None of thesharpened/tapered drug-delivery features described herein with respectto Example 4 perforated the vessel.

E. Example 5—Stents Having Square Drug-delivery Features Placed Near anAtheroma, Atherosclerotic Lesion, and/or Calcification

In this example, a stent having square or rectilinear drug-deliveryfeatures was placed within a blood vessel of a human cadaver. Followingplacement of the square drug-delivery feature stent, the vessel wasremoved from the patient, embedded in plastic, and sliced intocross-sections of a thickness suitable for histology. The cross-sectionswere stained using an H&E stain, imaged, and evaluated for thepositioning of the square drug-delivery feature stent in the vessel.

FIGS. 9A-9K include histology images taken after placement of the stenthaving the square drug-delivery features in a vessel of the cadaver. Forexample, FIG. 9A depicts a square drug-delivery feature having a widthof 248.47 μm and a depth of 292.40 μm. FIG. 9B depicts 22 squaredrug-delivery features either engaging with the neointima, pushing theneointima into the IEL, or engaging with a plaque having calcifications.FIG. 9C depicts square drug-delivery features engaging with theneointima, engaging with a plaque having calcifications, or engagingwith the non-calcified intima. FIG. 9D depicts square drug-deliveryfeatures engaging with the IEL and others penetrating the intima andmedia having calcifications. FIG. 9E depicts square drug-deliveryfeatures engaging with the IEL and others pushing the neointima into theIEL FIG. 9F depicts square drug-delivery features penetrating theneointima and others penetrating the media. FIG. 9G depicts squaredrug-delivery features engaging with a calcified atheroma, otherspenetrating the neointima, and another penetrating the media. FIG. 9H isa higher magnification of a portion of the atheroma depicted in FIG. 9G.FIG. 9I depicts square drug-delivery features engaging the neointima andthe media of a calcified atherosclerotic plaque. FIG. 9J is a highermagnification of a portion of the atheroma depicted in FIG. 9I. FIG. 9Kis a higher magnification of a portion of the atheroma depicted in FIG.9J. None of the drug-delivery features associated with Example 5perforated the vessel.

The above detailed descriptions of embodiments of the technology are notintended to be exhaustive or to limit the technology to the precise formdisclosed above. Although specific embodiments of, and examples for, thetechnology are described above for illustrative purposes, variousequivalent modifications are possible within the scope of thetechnology, as those skilled in the relevant art will recognize. Forexample, while steps are presented in a given order, alternativeembodiments may perform steps in a different order. The variousembodiments described herein may also be combined to provide furtherembodiments.

From the foregoing, it will be appreciated that specific embodiments ofthe technology have been described herein for purposes of illustration,but well-known structures and functions have not been shown or describedin detail to avoid unnecessarily obscuring the description of theembodiments of the technology. Where the context permits, singular orplural terms may also include the plural or singular term, respectively.

Moreover, unless the word “or” is expressly limited to mean only asingle item exclusive from the other items in reference to a list of twoor more items, then the use of “or” in such a list is to be interpretedas including (a) any single item in the list, (b) all of the items inthe list, or (c) any combination of the items in the list. Additionally,the term “comprising” is used throughout to mean including at least therecited feature(s) such that any greater number of the same featureand/or additional types of other features are not precluded. It willalso be appreciated that specific embodiments have been described hereinfor purposes of illustration, but that various modifications may be madewithout deviating from the technology. Further, while advantagesassociated with certain embodiments of the technology have beendescribed in the context of those embodiments, other embodiments mayalso exhibit such advantages, and not all embodiments need necessarilyexhibit such advantages to fall within the scope of the technology.Accordingly, the disclosure and associated technology can encompassother embodiments not expressly shown or described herein.

We claim:
 1. A method for treating a human patient with a stent, themethod comprising: intravascularly delivering the stent to a targettreatment site within a body lumen of the patient, wherein the stentcomprises— a radially expandable cylindrical frame having struts; aproximal end; a distal end; a lumen between the proximal end and thedistal end and providing a fluid pathway along a longitudinal axis ofthe frame; and protruding features carried by the struts; allowing thestent to self-expand from a low-profile delivery state to an expandeddeployed state; and expanding the stent with a mechanical actuationmechanism such that a first portion of each of the protruding featuresextends from the frame in a direction substantially parallel to thelongitudinal axis of the frame and a second portion of each of theprotruding features forms a terminal end that extends radially outwardlyaway from the frame, is positioned entirely distal to the first portion,and pierces through a wall of the body lumen, wherein the frame iscollapsible from the deployed state to the delivery state to beretracted within a catheter and withdrawn from the body lumen of thepatient.
 2. The method of claim 1 wherein, when the frame is in theexpanded state, the protruding features further extend radially outwardthrough the wall of the body lumen, through a first portion of the bodylumen, and extend into a second portion of the body lumen to deliver adrug thereto.
 3. The method of claim 1 wherein a first portion of thebody lumen is an occlusion, an intima, or a combination thereof, andwherein a second portion of the body lumen is a media, an adventitia, ora combination thereof.
 4. The method of claim 1 wherein the plurality ofprotruding features comprise a first set of protruding featuresconfigured to deliver a first drug to the patient and a second set ofprotruding features configured to deliver a second drug to the patient,and wherein the first drug and the second drug are the same drug ordifferent drugs.
 5. The method of claim 1 wherein the plurality ofprotruding features comprise reservoirs integrally formed therein and/orwherein the plurality of protruding features, the stent, or acombination thereof are coated with a substrate configured to deliver adrug carried therein to the patient, to prevent clotting, to preventocclusion of the stent, or a combination thereof.
 6. The method of claim1 further comprising delivering a drug to the patient from theprotruding features.
 7. The method of claim 1 wherein the protrudingfeatures are connected to each other only via the frame.
 8. The methodof claim 1 wherein each of the protruding features comprises a firstportion deployable to extend from the frame in a first direction and asecond portion deployable to extend radially outwardly in a seconddirection, different from the first direction and away from the frame.9. The method of claim 8 wherein the second portion of each protrudingfeature is connected to the frame only via the first portion.
 10. Themethod of claim 1 wherein the struts are connected to each other to forma circumferential ring that extends continuously about a longitudinalaxis of the frame.
 11. The method of claim 10, wherein each protrudingfeature extends from the circumferential ring and is axially offset fromthe circumferential ring.
 12. A method for treating a human patient witha stent, the method comprising: intravascularly delivering the stent toa target treatment site within a body lumen of the patient, wherein thestent comprises— a radially expandable cylindrical frame having struts;a proximal end; a distal end; a lumen between the proximal end and thedistal end and providing a fluid pathway along a longitudinal axis ofthe frame; and protruding features carried by the struts, each of theprotruding features comprising a first portion deployable to extend fromthe frame in a direction substantially parallel to a longitudinal axisof the frame and a second portion that forms a terminal end of thecorresponding protruding feature, is deployable to extend radiallyoutwardly away from the frame, and is positioned entirely distal to thefirst portion; allowing the stent to self-expand from a low-profiledelivery state to an expanded deployed state; and expanding the stentwith a mechanical actuation mechanism such that the second portion ofeach protruding feature pierces through a wall of the body lumen,wherein the frame is collapsible from the deployed state to the deliverystate to be retracted within a catheter and withdrawn from the bodylumen of the patient.
 13. The method of claim 12 further comprisingdelivering a drug to the patient from the protruding features.
 14. Themethod of claim 12 wherein the protruding features are connected to eachother only via the frame.
 15. The method of claim 12 wherein the secondportion of each protruding feature is connected to the frame only viathe first portion.
 16. The method of claim 12 wherein the struts areconnected to each other to form a circumferential ring that extendscontinuously about the longitudinal axis.
 17. The method of claim 16,wherein each protruding feature extends from the circumferential ringand is axially offset from the circumferential ring.